An Exploration of the Metal Oxide-assisted Decomposition and Rearrangement of N-Acyl-1,3-oxazolidin-2-ones Leading to 2-Aryl-2-oxazolines [1]

Abstract

An exploration into the utility of the thermally-induced (metal oxide-mediated) CO 2 extrusion and subsequent rearrangement of N-acyl-1,3-oxazolidin-2-ones to form 2-aryl(alkyl)-2-oxazolines is described. The reaction is found to give moderate yields of the corresponding 2-oxazolines. Attempts to employ the above methodology to give enantiopure (R)-or (S)-2,5-diphenyl-2-oxazoline (the latter form being the natural product Oxytriphine) from enantiopure (and crystallographically characterised) (S)-N-benzoyl-5-phenyl-2-oxazolidinone led to the isolation of an essentially racemic product. These protocols are compared to other common methods used to form the oxazoline ring system and are placed into context with previous investigations of such ring forming reactions.

The Crystal and Molecular Structure of (2Z)-2-[3-(4-Methoxybenzoyl)-4,4-dimethyl-1,2-oxazolidin-2-ylidene]-1-(4-methoxyphenyl)ethanone

“…In the case of Molecule A, the relative spacing and twisting of the two aromatic rings results in a longer C22A•••O3A distance (6.66 Å) than that observed for the same spacing in B (6.27 Å). The heterocyclic rings in both molecules display deviations from planarity of 9.7° (Molecule A) and 8.0° (Molecule B) [21] as measured by their respective N1-C1-O1-C3 torsion angles. The bond lengths observed (Table 1) for the various functional groups are well within the expected ranges for such bonds and hence are otherwise unsurprising [28].…”

“…The ring is also found in a number of natural products, many of which have been the subject of total synthesis. Examples of these include complex molecules such as Basilibactin A down to very simple small molecules such as Oxytriphine (1 and 2, respectively: Figure 1) [19][20][21]. Sometime ago, Tohda and co-workers presented [22] a facile two-step strategy for the synthesis of enol-containing oxazolines initiating from 2,4,4-trimethyl-2-oxazoline (3).…”